Dilated Cardiomyopathy (DCM) and Chronical Degenerative Valvular Disease (CDVD) are very common in dogs nowadays. However, due to modern level in oncology we can meet chemotherapy-induced cardiomyopathies more often. We have lack of information about pathogenic mechanisms underlying Doxorubicin-induced Cardiomyopathy (DoxCM) and features differentiating it from CDVD and DCM. In this study we investigate several metabolic features of doxorubicin-induced cardiomyopathy, DCM-like phenotype cardiomyopathies and CDVD. We observed some stages of myocardium glucose metabolism in order to estimate life potential of end stage myocardium and respectively survival of patient. The study population consisted of 46 dogs of different age, sex and breed. These dogs were subgrouped due to diagnosis: Healthy dogs without heart failure, DCM, CDVD and DoxCM. Fresh myocardial biopsies taken immediately after euthanasia from left ventricular apex, freezed in liquid nitrogen for ELISA and biochemical study. Differences in metabolic profile found between of CDVD and healthy dogs were not significant. At the same time doxorubicin induced cardiomyopathy and DCM-like phenotype myocardial disease had similar changes. It should be mentioned, DCM patients had previously long history of treatment, but DoxCM group-not. Differences between DoxCM, DCM and CDVD were significant and can be explained by changes what suffering myocardium undergoes. Rapid or slow developing energy depletion leads to myocardiocytes death and heart failure. Doxorubicin-induced cardiomyopathy is far more dangerous due to rapidness of development in observed study. Myocardium, due to lack of time, had no adapting ability for acute energy depletion and massive cell death. This preliminary study shows changes induced by doxorubicin (Dox) in dogs. These findings mostly connected with mitochondrial disturbances, insulin resistance and energy depletion. In this study also shown several features connected with development of CDVD and differences from DCM.
Background: Heart failure syndrome is an aspect of primary or secondary heart disease and is associated with decompensation, formation, and activation of pathological interactions between regulation systems. This results in myocardial energy metabolism alteration. This study was carried out to defy some metabolic aspects of myocardial tissue insulin resistance (IRM) development in canine heart failure.Aim: To investigate the myocardial tissue concentration of adenosine triphosphate (ATP), glucose transporters 1 and 4, pyruvate dehydrogenase (PDH), hexokinase 2, insulin receptor (InsR), and adropin (ADR) protein and to screen metabolic changes and IRM in canine myocardium with heart failure.Methods: We studied 28 dogs of different sexes, ages, and breeds. Groups were formed according to primary pathology: apparently healthy dogs (HD, n = 6); dogs with CDVD (CDVDD, n = 8); dogs with DCM (DCMD, n = 6); and dogs with doxorubicin chemotherapy and doxorubicin-induced cardiomyopathy (DoxCMD, n = 8). Animals in the study were diagnosed for primary disease by standard methods and algorithms. Animals were euthanized due to incurable neurological disease, refractory heart failure, or by owners will. The material was obtained immediately after death, fixed in liquid nitrogen, and stored in −80°C refrigerator. Studied proteins concentrations were analyzed in a specialized research laboratory, using ELISA kits, provided by Cloud-Clone Corp.Results: ATP, GLUT1, and GLUT4 concentrations in myocardial tissue from the valvular disease group did not differ from the HD group. In CDVD, we found depression of PDH, hexokinase II (HX2), and ADR concentrations in comparison to HD. InsR was significantly lower in the CDVD and DoxCMD groups in comparison to the HD group, but in the DCM group, it was twofold higher than in the HD group. In the DCMD and DoxCMD groups, all parameters were lower than in the HD group. ATP, HX2, ADR, GLUT1, and GLUT4 were higher in the CDVD group, than in the DCM and DoxCM groups. PDH in the CDVD and DoxCM groups did not differ. PDH was depleted in the DCM to CDVD and DoxCM groups. InsR did not differ between the CDVD and DoxCM groups, but was upregulated in the DCM to CDVD and DoxCM groups.Conclusion: Development of myocardial tissue IRM is a part of the structural, functional and metabolic remodeling in dogs with heart failure of different etiology. At the late stages, we found significant changes in energy supply availability and production in the myocardium.
Dilated Cardiomyopathy (DCM) and Chronical Degenerative Valvular Disease (CDVD) are very common in dogs nowadays. However, due to modern level in oncology we can meet chemotherapy-induced cardiomyopathies more often. We have lack of information about pathogenic mechanisms underlying doxorubicin-induced cardiomyopathy (DoxCM) and features differentiating it from CDVD and DCM. The study population consisted of 46 dogs of different age, sex and breed. These dogs were sub grouped due to diagnosis: Healthy dogs without heart failure (n = 14), DCM (n = 6), CDVD (n = 16) and DoxCM (n = 10). Fresh myocardial biopsies taken immediately after euthanasia from left ventricular apex, freezed in liquid nitrogen for biochemical study and prepared for histological and electron microscopy. Histological and ultrastructural findings defined several features connected with pathogenesis of different diseases. This preliminary study shows changes induced by Doxorubicin (Dox) in dogs. These findings mostly connected with mitochondrial disturbances, insulin resistance and energy depletion. In this study also shown several features connected with development of CDVD and differences from DCM.
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